Since the introduction of the National Institute for Health and Care Excellence (NICE) guidelines on thromboprophylaxis and the use of extended thromboprophylaxis with new oral agents, there have been reports of complications arising as a result of their use. We have looked at the incidence of wound complications after the introduction of dabigatran for thromboprophylaxis in our unit. We investigated the rate of venous thromboembolism and wound leakage in 1728 patients undergoing primary joint replacement, both before and after the introduction of dabigatran, and following its subsequent withdrawal from our unit. We found that the use of dabigatran led to a significant increase in post-operative wound leakage (20% with dabigatran, 5% with a multimodal regimen; p < 0.001), which also resulted in an increased duration of hospital stay. The rate of thromboembolism in patients receiving dabigatran was higher (1.3%) than in those receiving the multimodal thromboprophylaxis regimen, including low molecular weight heparin as an inpatient and the extended use of aspirin (0.3%, p = 0.047). We have ceased the use of dabigatran for thromboprophylaxis in these patients. Cite this article: Bone Joint J 2014;96-B:122–6

Background. Hitherto, no study has compared blood loss (BL) after different thromoprophylactic regimes (TR). The objective of this study was to quantify and compare BL in total hip arthroplasty (THA) under three different TRs. Methods. Between September 2013 and July 2014, sixty primary, unilateral, same-implant THAs entered a randomised, double-blind clinical trial. The patients were randomised to receive manufacturers' recommended doses of enoxaparin, dabigatran or rivaroxaban. Complete blood counts were obtained preoperatively and on the third day postoperatively. BL was calculated according to the Nadler formula. We also evaluated the occurence of wound healing disturbances (WHDs). All data were analysed using R statistical software. Results. The mean BL and standard deviations were 844 ± 222 ml for enoxaparin, 854 ± 205 ml for dabigatran and 806 ± 227 ml for rivaroxaban. The BL did not significantly differ between groups (Kruskall-Wallis, p=0.92). More WHDs occured in the rivaroxaban group (5/20), compared to enoxaparin (2/20) and dabigatran (3/20). Conclusions. None of the chemical TR is superior to others in terms of reducing the BL. There seems to be more WHDs with the use of oral agents - this finding needs further studies. Level of evidence. 1b (Centre for Evidence Based Medicine, Oxford). Approval. This study was approved by The Medical Centre of Postgraduate Education Ethical Committee. Disclosure. The authors disclose no competing interests

BACKGROUND: Oral DVT prophylaxis not requiring monitoring is an advantage in orthopaedic patients. Dabigatran etexilate is an oral direct thrombin inhibitor undergoing evaluation for the prevention of venous thromboembolic events (VTE) following orthopaedic surgery. METHODS: In a phase III, multicenter, non-inferiority, double-blind study, patients undergoing total knee replacement were randomized to 3 treatments. The patients received 8±2 days of oral dabigatran etexilate, 150 or 220 mg once daily starting with a half dose (i.e.75 or 110 mg) 1–4 hours after surgery, or subcutaneous enoxaparin 40 mg once daily starting 12 hours prior to surgery. The primary efficacy outcome was the composite of total VTE and all causes of mortality during the treatment period. All efficacy and safety outcome events were adjudicated by blinded independent committees. RESULTS: Efficacy could be evaluated for 1541 (75%) treated and operated patients. Total VTE and death occurred in 40.5%, 36.4% and 37.7% of patients assigned to dabigatran etexilate 150 or 220mg once daily or enoxaparin, respectively. Proximal DVT and/ or PE occurred in 3.8%, 2.6% and 3.5% of patients receiving dabigatran 150 or 220mg or enoxaparin, respectively. Three deaths occurred during the treatment period, one in each of the treatment groups. Safety was evaluated for all 2076 patients receiving study treatment. The rate of major bleeding was 1.3%, 1.5% and 1.3% of patients receiving dabigatran 150 or 220mg or enoxaparin. Elevated LFTs (ALT > 3xULN) occurred in 3.7%, 2.8% and 4.0% of the patients treated with 150 and 220 mg dabigatran or enoxaparin during the study. A temporary rise in LFTs was observed during the follow-up period in 0.5% of the patients who had received dabigatran and in 0.4% of the patients who had received enoxaparin. CONCLUSIONS: Non-inferiority for the primary efficacy endpoint was met for both doses of dabigatran etexilate compared to enoxaparin. There was no difference in bleeding rates between the treatment groups. Oral administration of dabigatran etexilate once daily, given early in the postoperative period, was effective and safe for the prevention of total VTE in patients undergoing total knee replacement surgery

NICE technology appraisal guidance 157 suggests that the oral anticoagulation medication Dabigatran etexilate (Pradaxa®, Boehringer Ingelheim) can be used for the primary prevention of venous thromboembolic events (VTE's) in adult patients who have undergone elective total hip (THR) or knee replacement (TKR) surgery. The NICE guidance and the Pradaxa® Summary of Product characteristics (SPC) report that 13.8% of patients receiving recommended doses of Dabigatran experience adverse bleeding events. In the manufacturer's pivotal clinical trials, wound secretion accounted for 4.9% of patients treated with Dabigatran as compared to 3.0% treated with Enoxaparin. The aim of this audit was to assess the impact of Dabigatran on wound complications at a UK district general hospital and to quantify the effect on the postoperative discharge home support services provided by the award-winning South Warwickshire Accelerated Transfer Team (SWATT). We report our experience of Dabigatran use at Warwick Hospital from March 2009 to March 2010. Of the 788 lower limb arthroplasties performed, 681 patients (81.0%) were accepted for SWATT follow-up. Fifty-five (8.6%) of patients accepted by SWATT showed increased wound secretion for greater than 5 days. This included 12.7% of THR and 5.5% of TKR patients. Increased wound secretion resulted in 226 extra home visits by SWATT, at an extra cost of £23,104 (7.5% increase in SWATT budget). Twenty-six of the 55 patients had positive microbial growth when wound secretions were swabbed. Five patients were admitted for management of wound infections. Incidentally, there were 2 reported cases of DVT and PE. These were not in the increased wound secretion patients. In summary, Dabigatran at Warwick Hospital was associated with a higher than predicted incidence of surgical site morbidity, increased resource output and increased postoperative discharge costs. As a consequence, Dabigatran use has been reduced and other oral anticoagulants are being trialled

NICE technology appraisal guidance 157 suggests that the oral anticoagulation medication Dabigatran etexilate can be used for the primary prevention of venous thromboembolic events (VTE's) in adult patients who have undergone elective total hip or knee replacement surgery. The NICE guidance reports that 13.8% of patients receiving recommended doses of Dabigatran experienced adverse bleeding events. In the pivotal hip and knee VTE trial, wound secretion only accounted for 4.9% of patients treated with Dabigatran (cf 3.0% of patients treated with Enoxaparin). We report our wound secretion experience after Dabigatran use at Warwick Hospital from March 2009 to March 2010. Of the 788 lower-limb arthroplasties performed, 55 patients (6.9%) had oozing wounds after discharge (Mean=8 days, Range=1-39 days). This resulted in 226 extra home-visits by discharge nurses, 26 positive microbiology cultures and 5 confirmed wound infections needing antibiotic treatment and/or surgical intervention. Incidentally, there were also 2 known cases each of deep vein thrombosis and pulmonary embolus in this cohort. The number of complications was markedly increased from previous years when LMWH was the VTE prophylaxis used. This data suggests that the use of Dabigatran in Warwick Hospital may significantly increase surgical site morbidity and resource output after lower limb arthroplasty

In recent years, many changes have taken place regarding agents used for chemical thromboprophylaxis in elective joint replacement. Enoxaparin, Rivaroxaban, Dabigatran and Apixaban are all now recommended in NICE CG92 and their use varies nationally. Whilst data exists comparing oral anticoagulants to Enoxaparin, there is little data on the comparative efficacy of the individual oral anticoagulants. This study analyses data from Warrington Hospital, where each of the above oral anticoagulants was used trustwide in 3 successive years following hip and knee arthroplasty. We analysed similar 4–5 month periods in 2010(Rivaroxiban), 2011(Dabigatran) and 2012(Apixaban). The study was done prospectively and data was collected contemporaneously. The total sample size was 475 patients. Data was collected through electronic hospital patient records. Patients were excluded if data was incomplete. We defined our primary outcome as any complication requiring the drug to be omitted or stopped. We found that for Rivaroxaban, 7 of 129 patients had the drug omitted or stopped (5.4%, 95% confidence interval 1.0–9.8), for Dabigatran 19 of 150 patients, (12.7%, 95% confidence interval 6.4–19.0) and for Apixaban 10 of 196 patients (5.1%, 95% confidence interval 0.9–9.3). For Rivaroxaban and Apixaban, there were no confirmed thromboembolic events; however, for Dabigatran, there were six VTEs. All three had bleeding complications, which were well below the figures published for Enoxaparin. Apixaban registered the lowest rate in our study (5.1%). This data suggests that Apixaban is a safe oral anticoagulant in elective total knee and hip replacement

The introduction of direct thrombin inhibitors in arthroplasty surgery has reignited the debate on the risk of wound complications when using chemical thromboprophylaxis. It has been suggested that direct thrombin inhibitors might lead to an increased risk of systemic and operative site bleeding and wound sepsis when compared to low molecular weight heparin. In July 2009, departmental thromboprophylaxis policy for patients undergoing hip and knee replacement surgery (including revision) was changed from subcutaneous enoxaparin for the duration of inpatient stay to dabigatran for 10 days (knees) or 28 days (hips) unless contraindicated. In the 2 years prior to policy change, 1091 patients underwent hip or knee arthroplasty (Group A), with 1150 patients undergoing the same procedures in the 2 years following July 2009 (Group B). A minority of patients were already on warfarin (2% in group 1, 3% in group 2). This study presents a retrospective analysis of all patients who returned to theatre within 30 days of joint replacement surgery to assess whether the change in unit policy caused any discernible increase in bleeding-related complications. In group A, 20 / 1091 patients (1.8%) returned to theatre within 30 days. 9 were for reasons unrelated to thromboprophylaxis (mainly dislocated hips), 4 for gastrointestinal bleeding and 7 for wound complications (haematoma, wound breakdown, or infection). In group B, 22 / 1150 patients (1.9%) returned to theatre within 30 days. 13 were for unrelated reasons, 4 for gastrointestinal bleeding, and 5 for wound complications. One patient with a wound complication was on warfarin and therefore did not receive dabigatran. The lower wound complication rate in group B was not statistically different. This study, in a large heterogeneous group of patients, suggests that a change from enoxaparin to dabigatran does not increase the incidence of early infection, or the risk of bleeding at the operative site or the gastrointestinal tract

The introduction of direct thrombin inhibitors in arthroplasty surgery has reignited the debate on the risk of wound complications when using chemical thromboprophylaxis. It has been suggested that direct thrombin inhibitors might lead to an increased risk of systemic and operative site bleeding and wound sepsis when compared to low molecular weight heparin. In July 2009, departmental thromboprophylaxis policy for patients undergoing hip and knee replacement surgery (including revision) was changed from subcutaneous enoxaparin for the duration of inpatient stay to dabigatran for 10 days (knees) or 28 days (hips) unless contraindicated. In the 2 years prior to policy change, 1091 patients underwent hip or knee arthroplasty (Group A), with1150 patients undergoing the same procedures in the 2 years following July 2009 (Group B). A minority of patients were already on warfarin (2% in group 1, 3% in group 2). This study presents a retrospective analysis of all patients who returned to theatre within 30 days of joint replacement surgery to assess whether the change in unit policy caused any discernible increase in bleeding-related complications. In group A, 20/1091 patients (1.8%) returned to theatre within 30 days. 9 were for reasons unrelated to thromboprophylaxis (mainly dislocated hips), 4 for gastrointestinal bleeding and 7 for wound complications (haematoma, wound breakdown, or infection). In group B, 22/1150 patients (1.9%) returned to theatre within 30 days. 13 were for unrelated reasons, 4 for gastrointestinal bleeding, and 5 for wound complications. One patient with a wound complication was on warfarin and therefore did not receive dabigatran. The lower wound complication rate in group B was not statistically different. This study, in a large heterogeneous group of patients, suggests that a change from enoxaparin to dabigatran does not increase the incidence of local or systemic complications of sufficient severity to warrant return to theatre

Aims. NICE recommends oral anticoagulants after lower limb arthroplasty, as they are thought to lead to better outpatient compliance than injected anticoagulants. Having prescribed self-administered Dalteparin for many years, we began using oral Dabigatran in December 2010. The change afforded an opportunity to compare compliance and acceptability of the two treatments. Methods. Patients were recruited at discharge and telephoned at 28 days. Left over doses were counted to assess compliance. Side-effects, complications and patient views were also recorded. Results. 47 patients were discharged on dalteparin, 59 on dabigatran. Total compliance rates were 81% and 56% respectively (p<0.001). However, the mean pain score associated with dalteparin was 2.4 out of 10, and 31% of patients experienced significant bruising. No patient suffered pain or bruising with dabigatran (p<0.001), but two experienced dyspepsia and four suffered wound problems. Two thromboembolic events and one gastrointestinal bleed occurred in the dalteparin group. Conclusions. Our outpatient compliance is higher for injected anticoagulants than for oral anticoagulants. This runs contrary to some of the marketing for oral agents. However, Dabigatran offers better patient acceptability than Dalteparin. While not designed or powered to show statistically significant differences in complication rates, our study has prompted closer investigation of wound problems with both treatments

Dabigatran etexilate (Pradaxa. ®. ) is an oral direct thrombin inhibitor that was recently approved in Europe and Canada for the prevention of venous thromboembolism (VTE) in patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA) surgery. In the phase III studies, concomitant administration of selective nonsteroidal anti-inflammatory drugs (NSAIDs with t½≤12 hours) and acetylsalicylic acid (ASA; < 160 mg/day) was allowed during treatment with dabigatran etexilate or enoxaparin. Due to the potential additional anticoagulant activity of these concomitant therapies a separate post hoc analysis was conducted to investigate the bleeding risk in these patients. We analysed the pooled study population (8,135 patients) from the three phase III trials in THA and TKA surgery (RE-MOBILIZE, RE-MODEL and RE-NOVATE) for major bleeding events (MBE). All MBE, which included surgical site bleeds, were assessed by an independent, expert adjudication committee. We report the rates of MBE and odds ratios (with 95% confidence intervals [CI]) for comparison of the subgroup concomitantly treated with NSAID (or ASA) versus the subgroup of patients without concomitant antithrombotically active medication. The overall rate of MBE (with and without NSAIDs and ASA) was 1.4% [CI 1.0–1.9], 1.1% [0.7–1.5] and 1.4% [1.0–2.0] with dabigatran etexilate 220 mg, 150 mg, and enoxaparin, respectively. Of the total population, 57.4% of patients received concomitant antithrombotic treatment: 54.1% received NSAID and 4.7% received ASA. The MBE rate in patients receiving dabigatran etexilate or enoxaparin plus NSAIDs was similar to the rate in patients taking only dabigatran etexilate or enoxaparin; 1.5% vs. 1.4% [OR 1.05; 0.55–2.01] for dabigatran etexilate 220 mg, 1.1% vs. 1.0% [OR 1.19; 0.55–2.55] for dabigatran etexilate 150 mg, and 1.6% vs. 1.2% [OR 1.32; 0.67–2.57] for enoxaparin. A similar pattern was seen in patients concomitantly receiving ASA; in this small group only a few patients with MBE were observed: 2 (1.6%) in the dabigatran etexilate 220 mg group, 2 (1.6%) in the 150 mg group, and 4 (3.0%) in the enoxaparin group. No relevant differences in risk for MBE were detected between treatments by co-medication subgroup or within treatment groups when comparing patients receiving dabigatran etexilate or enoxaparin only versus those concomitantly receiving NSAIDs or ASA. In conclusion, patients concomitantly receiving dabigatran etexilate and NSAIDs (with t½ ≤12 hours) or ASA (< 160 mg/day) have a similar risk of MBE to patients taking only dabigatran etexilate. These data support the use of dabigatran etexilate for the prevention of VTE in patients after THA or TKA, when concomitant use of NSAIDs or ASA (< 160 mg/day) is required

In recent years, many changes have taken place regarding agents used for chemical thromboprophylaxis in elective joint replacement. Enoxaparin, Rivaroxaban, Dabigatran and Apixaban are all now recommended in NICE CG92 and their use varies nationally. While data exist comparing oral anticoagulants to Enoxaparin, there is little data on the comparative efficacy of the individual oral anticoagulants. This study analyses data from Warrington Hospital, where each of the above oral anticoagulants was used trustwide in 3 successive years following hip and knee arthroplasty. We analysed similar 4–5 month periods in 2010 (Rivaroxiban), 2011 (Dabigatran) and 2012 (Apixaban). The study was done prospectively and data was collected contemporaneously. The total sample size was 475 patients. Data was collected through electronic hospital patient records. Patients were excluded if data was incomplete. We defined our primary outcome as any complication requiring the drug to be omitted or stopped. We found that for Rivaroxaban, 7 of 129 patients had the drug omitted or stopped (5.4%, 95% confidence interval 1.0–9.8), for Dabigatran 19 of 150 patients, (12.7%, 95% confidence interval 6.4–19.0) and for Apixaban 10 of 196 patients (5.1%, 95% confidence interval 0.9–9.3). For Rivaroxaban and Apixaban, there were no confirmed thromboembolic events; however, for Dabigatran, there were six VTEs. All three had bleeding complications, which were well below the figures published for Enoxaparin. Apixaban registered the lowest rate in our study (5.1%). This data suggests that Apixaban is a safe oral anticoagulant in elective total knee and hip replacement

Dabigatran etexilate (Pradaxa. ®. ) is an oral anticoagulant licensed in multiple countries, Europe and Canada, for the prevention of venous thromboembolic events (VTE) in patients undergoing total hip replacement surgery (THR) or total knee replacement surgery (TKR). The label recommendation for therapy initiation of dabigatran etexilate is a half dose given 1–4 hours after surgery. If this is not possible, then dabigatran etexilate should be started the day following surgery with the full dose. In the European pivotal Phase III clinical trials, this initial dosing was delayed until the day after surgery in 14% of the cases. This prompted a post hoc study to analyze if these patients received adequate thromboprophylaxis. Pooled efficacy data of major VTE events (composite of proximal DVT, symptomatic DVT, pulmonary embolism and VTE-related death) from the two European pivotal trials (RE-MODEL; . Eriksson BI et al. . J Thromb Haemost. 2007. ;. 5. :. 2178. –2185. , and RENOVATE; . Eriksson BI et al. . Lancet. 2007. ;. 370. :. 949. –956. ) where analyzed. The group with delayed dosing was compared to the group that received therapy initiation on the day of surgery to determine if there was any significant effect on clinical outcome. The final decision on the timing of the administration of the first dose required sometimes clinical judgment, and in particular good haemostasis had to be present. Therefore, the bleeding rate and the timing of the first dose are confounded and an analysis of bleeding events was not performed. The major VTE rate in the group with delayed treatment initiation compared with the 1–4 hour post surgery treatment initiation group were 2.2% (95% CI: 0.1–4.4) vs. 3.0% (95% CI: 2.0–3.9) for 220 mg dabigatran etexilate, 8.3% (95% CI: 4.3–12.4) vs. 3.5% (95% CI 2.5–4.5) for 150 mg dabigatran etexilate, and 4.3% (95% CI 1.2–7.4) vs. 3.7% (95% CI 2.7–4.8) for 40 mg enoxaparin. As the confidence intervals overlap markedly, no statistically significant differences where found. In conclusion, no difference in the rates of major VTE and VTE related mortality was seen when the doses of dabigatran etexilate were postponed to the first postoperative day. These data need to be interpreted carefully due to the low number of patients in the delayed treatment group. As recommended in the current labelling of dabigatran etexilate, treatment should be initiated 1–4 hours post-surgery

The oral direct thrombin inhibitor dabigatran etexilate (Pradaxa. ®. ) was recently approved in Europe for the prevention of venous thromboembolism (VTE) in patients undergoing elective total knee or total hip replacement surgery. In the Phase III RE-MODEL (. Eriksson BI et al. . J Thromb Haemost. 2007. ; . 5. : . 2178. –2185. ) and RENOVATE (. Eriksson BI et al. . Lancet. 2007. ; . 370. : . 949. –956. ) clinical trials the safety and efficacy of 220 mg and 150 mg dabigatran etexilate once daily were studied. In both trials these doses were compared with 40 mg subcutaneous enoxaparin. A post hoc pooled analysis was performed in patients with moderate renal impairment (glomerular filtration rate ≥ 30 and < 50 ml/min) who participated in these two trials. The primary efficacy endpoint in both studies and the post hoc analysis was total VTE and all cause mortality; the key pre-specified secondary efficacy endpoint was major VTE and VTE-related mortality. Bleeding events (the primary safety endpoint) were blindly adjudicated and categorised as major bleeding events (MBE), which includes surgical site bleedings. A total of 1825 patients were treated with 220 mg dabigatran etexilate, 1866 with 150 mg dabigatran etexilate and 1848 with 40 mg enoxaparin. Of these, 337 patients had moderate renal impairment. 68% of these patients could be evaluated for the primary efficacy endpoint, 72% for the secondary efficacy endpoint, and all patients were included in the safety and bleeding analyses. The incidence of total VTE and all cause mortality was 17.7% (14/79), 23.5% (16/68) and 27.8% (25/90) in the 220 mg dabigatran etexilate, 150 mg dabigatran etexilate and enoxaparin groups, respectively. When the secondary efficacy endpoint was analysed a similar trend was seen, with a descriptive statistical significance for a lower event rate in the 220 mg group: 1.2% (1/83; p=0.04 vs enoxaparin using Fisher’s exact test), 4.3% (3/70) with 150 mg dabigatran etexilate; and 9.0% (8/89) in the enoxaparin group. MBE occurred in 6/113 patients (5.3%) in the 220 mg dabigatran etexilate-treated group, in none of the patients in the 150 mg dabigatran etexilate-treated group (0/96; p=0.04 vs enoxaparin using Fisher’s exact test), and in 6/128 patients (4.7%) receiving enoxaparin. Of note, 3/6 MBE in the 220 mg group started before oral dabigatran etexilate treatment was initiated. In conclusion, oral 150 mg dabigatran etexilate showed similar efficacy compared with subcutaneous enoxaparin in patients with moderate renal impairment undergoing hip or knee replacement surgery, with an apparently lower rate of major bleeding. As bleeding is a major concern, especially in this population, the 150 mg once daily dose of dabigatran etexilate is currently recommended by EMEA for this group

We present the 12 month data on the relatively novel drug Dabigatran Etexilate (Pradaxa), a new oral anticoagulant which was introduced to combat the risk of post operative venous-thromboembolic disease (VTED) in orthopaedic surgery. This drug was introduced at our hospital in March 2010 and we present our modified protocol of: using 5000u subcutaneous Dalteparin whilst in hospital and giving Dabigatran only on discharge, and at a lower dose (150mg compared to 220mg). We carried out a retrospective analysis of the notes and imaging of every patient who underwent elective hip and knee arthroplasty over 12 months since the drug was introduced. We evaluated the rate of VTED complications and the rate of transfusion and bleeding post operatively. The case series of 370 patients showed a 1% risk of deep vein thrombosis with no pulmonary emboli and 1 death due to an unrelated cause. There was a transfusion rate of 11% with 0.5% patients taken back to theatre for evacuation of haematomas. There were no reported adverse effects of Dabigatran. We argue that our modified protocol for this novel drug should be followed as it is both safe and effective for postoperative anticoagulation

The introduction of direct thrombin inhibitors in arthroplasty surgery has reignited the debate on the risk of wound complications when using chemical thromboprophylaxis. It has been suggested that direct thrombin inhibitors might lead to an increased risk of systemic and operative site bleeding and wound sepsis when compared to low molecular weight heparin. In July 2009, departmental thromboprophylaxis policy for patients undergoing hip and knee replacement surgery (including revision) was changed from subcutaneous enoxaparin for the duration of inpatient stay to dabigatran for 10 days (knees) or 28 days (hips) unless contraindidated. In the 2 years prior to policy change, 1091 patients underwent hip or knee arthroplasty (Group 1), with1150 patients undergoing the same procedures in the 2 years following July 2009 (Group 2). A minority of patients were already on warfarin (2% in group 1, 3% in group 2). This study presents a retrospective analysis of all patients who returned to theatre within 30 days of joint replacement surgery to assess whether the change in unit policy caused any discernible increase in bleeding-related complications. In group 1, 23/1091 patients (2.1%) returned to theatre within 30 days. 8 were for reasons unrelated to thromboprophylaxis (mainly dislocated hips), 5 for gastrointestinal bleeding (mainly upper GI endoscopy) and 10 for wound complications (haematoma, wound breakdown, or washout of early infection). In group 2, 22 / 1150 patients (1.9%) returned to theatre within 30 days. 12 were for unrelated reasons, 5 for GI bleeding, and 5 for wound complications. The lower return to theatre rate in the second group was not statistically different. This study, in a large heterogeneous group of patients, suggests that a change from enoxaparin to dabigatran does not increase the incidence of early infection, or the risk of bleeding at the operative site or the gastrointestinal tract

Dabigatran etexilate (Pradaxa. ®. ) is an oral direct thrombin inhibitor that was recently approved in Europe and Canada for the prevention of venous thromboembolism (VTE) in patients undergoing elective total knee replacement or total hip replacement surgery. Two pivotal clinical trials, RE-MODEL (. Eriksson BI et al. . J Thromb Haemost. 2007. ; . 5. : . 2178. –2185. ) and RENOVATE (. Eriksson BI et al. . Lancet. 2007. ; . 370. : . 949. –956. ), studied the efficacy and safety of 220 mg and 150 mg dabigatran etexilate once daily compared with 40 mg subcutaneous enoxaparin. A post hoc pooled analysis was performed in elderly patients (> 75 years) since renal function gradually declines with age. The primary efficacy endpoint was total VTE and all cause mortality and the secondary efficacy endpoint was major VTE and VTE-related mortality. The primary safety endpoint was major bleeding events (MBE), including those occurring at the surgical site. All bleeding events were blindly adjudicated. Of the patients treated with 220 mg dabigatran etexilate (n=1825), 150 mg dabigatran etexilate (n=1866) and enoxaparin (n=1848), 883 patients (16%) were over 75 years. 73% of these elderly patients were evaluable for the primary efficacy endpoint and 75% were evaluable for the secondary efficacy endpoint. All patients > 75 years were evaluable for safety outcomes, including bleeding. The incidence of total VTE and all cause mortality was 20.8% (44/212), 22.6% (49/217), and 27.2% (58/213), respectively, in the three groups. A similar trend was observed for major VTE and VTE-related mortality: 220 mg dabigatran etexilate, 1.9% (4/216, p=0.045 vs enoxaparin using Fisher’s exact test); 150 mg dabigatran etexilate, 4.5% (10/221); enoxaparin, 6.0% (13/218). MBE occurred in 11 of the 295 elderly patients receiving 220 mg dabigatran etexilate (3.7%), 4 of the 282 elderly patients receiving 150 mg dabigatran etexilate (1.4%) and in 9 of the 306 elderly patients taking enoxaparin (2.9%). Notably, 6/11 MBE in the dabigatran 220 mg group and 2/4 MBE in the 150 mg group started before the first dose of treatment. We conclude that in elderly patients (> 75 years) undergoing hip or knee replacement surgery, oral 150 mg dabigatran etexilate exhibited a numerically favourable bleeding profile with no difference in efficacy compared with 40 mg enoxaparin. Because safety, particularly bleeding, is of paramount importance in the elderly, the 150 mg once daily dose of dabigatran etexilate is currently recommended by EMEA for this group

This paper reports the cost of outpatient venous thromboembolism (VTE) prophylaxis following 388 injuries of the lower limb requiring immobilisation in our institution, from a total of 7408 new patients presenting between May and November 2011. Prophylaxis was by either self-administered subcutaneous dalteparin (n = 128) or oral dabigatran (n = 260). The mean duration of prophylaxis per patient was 46 days (6 to 168). The total cost (pay and non-pay) for prophylaxis with dalteparin was £107.54 and with dabigatran was £143.99. However, five patients in the dalteparin group required nurse administration (£23 per home visit), increasing the cost of dalteparin to £1142.54 per patient. The annual cost of VTE prophylaxis in a busy trauma clinic treating 12 700 new patients (2010/11), would be £92 526.33 in the context of an income for trauma of £1.82 million, which represents 5.3% of the outpatient tariff. Outpatient prophylaxis in a busy trauma clinic is achievable and affordable in the context of the clinical and financial risks involved. Cite this article: Bone Joint J 2013;95-B:673–7

Aims. We investigated the efficacy and safety profile of commonly used venous thromboembolism (VTE) prophylaxis agents following hip and knee arthroplasty. Methods. A systematic search of PubMed, Embase, Cochrane Library, Web of Science, and OrthoSearch was performed. Prophylaxis agents investigated were aspirin (< 325 mg and ≥ 325 mg daily), enoxaparin, dalteparin, fondaparinux, unfractionated heparin, warfarin, rivaroxaban, apixaban, and dabigatran. The primary efficacy outcome of interest was the risk of VTE, whereas the primary safety outcomes of interest were the risk of major bleeding events (MBE) and wound complications (WC). VTE was defined as the confirmed diagnosis of any deep vein thrombosis and/or pulmonary embolism. Network meta-analysis combining direct and indirect evidence was performed. Cluster rank analysis using the surface under cumulative ranking (SUCRA) was applied to compare each intervention group, weighing safety and efficacy outcomes. Results. Of 86 studies eligible studies, cluster rank analysis showed that aspirin < 325 mg daily (SUCRA-VTE 89.3%; SUCRA-MBE 75.3%; SUCRA-WC 71.1%), enoxaparin (SUCRA-VTE 55.7%; SUCRA-MBE 49.8%; SUCRA-WC 45.2%), and dabigatran (SUCRA-VTE 44.9%; SUCRA-MBE 52.0%; SUCRA-WC 41.9%) have an overall satisfactory efficacy and safety profile. Conclusion. We recommend the use of either aspirin < 325 mg daily, enoxaparin, or dabigatran for VTE prophylaxis following hip and knee arthroplasty. Cite this article: Bone Joint J 2024;106-B(9):924–934

Aims. The aim of this study is to compare the effectiveness and safety of thromboprophylactic treatments in patients undergoing primary total knee arthroplasty (TKA). Methods. Using nationwide medical registries, we identified patients with a primary TKA performed in Denmark between 1 January 2013 and 31 December 2018 who received thromboprophylactic treatment. We examined the 90-day risk of venous thromboembolism (VTE), major bleeding, and all-cause mortality following surgery. We used a Cox regression model to compute hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome, pairwise comparing treatment with dalteparin or dabigatran with rivaroxaban as the reference. The HRs were both computed using a multivariable and a propensity score matched analysis. Results. We identified 27,736 primary TKA patients who received thromboprophylactic treatment (rivaroxaban (n = 18,846); dalteparin (n = 5,767); dabigatran (n = 1,443); tinzaparin (n = 1,372); and enoxaparin (n = 308)). In the adjusted multivariable analysis and compared with rivaroxaban, treatment with dalteparin (HR 0.68 (95% CI 0.49 to 0.92)) or dabigatran (HR 0.31 (95% CI 0.13 to 0.70)) was associated with a decreased risk of VTE. No statistically significant differences were observed for major bleeding or all-cause mortality. The propensity score matched analysis yielded similar results. Conclusion. Treatment with dalteparin or dabigatran was associated with a decreased 90-day risk of VTE following primary TKA surgery compared with treatment with rivaroxaban. Cite this article: Bone Joint J 2021;103-B(10):1571–1577

Aims. There is uncertainty regarding the optimal means of thromboprophylaxis following total hip and knee arthroplasty (THA, TKA). This systematic review presents the evidence for acetylsalicylic acid (aspirin) as a thromboprophylactic agent in THA and TKA and compares it with other chemoprophylactic agents. Materials and Methods. A search of literature published between 2004 and 2014 was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 13 studies were eligible for inclusion. Results. Evidence from one good quality randomised controlled trial (RCT) showed no difference in rates of venous thrombo-embolism (VTE) in patients given aspirin or low molecular weight heparin (LMWH) following TKA. There was insufficient evidence from trials with moderate to severe risk of bias being present to suggest aspirin is more or less effective than LMWH, warfarin or dabigatran for the prevention of VTE in TKA or THA. Compared with aspirin, rates of asymptomatic deep vein thrombosis (DVT) in TKA may be reduced with rivaroxaban but insufficient evidence exists to demonstrate an effect on incidence of symptomatic DVT. Compared with aspirin there is evidence of more wound complications following THA and TKA with dabigatran and in TKA with rivaroxaban. Some studies highlighted concerns over bleeding complications and efficacy of aspirin. Conclusion. The results suggest aspirin may be considered a suitable alternative to other thromboprophylactic agents following THA and TKA. Further investigation is required to fully evaluate the safety and efficacy of aspirin. Cite this article: Bone Joint J 2016;98-B:1056–61